CXCL5 limits macrophage foam cell formation in atherosclerosis
Anthony Rousselle, … , Amrita Ahluwalia, Johan Duchene
Anthony Rousselle, … , Amrita Ahluwalia, Johan Duchene
Published February 8, 2013
Citation Information: J Clin Invest. 2013;123(3):1343-1347. https://doi.org/10.1172/JCI66580.
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Brief Report Cardiology

CXCL5 limits macrophage foam cell formation in atherosclerosis

Abstract

The ELR+-CXCL chemokines have been described typically as potent chemoattractants and activators of neutrophils during the acute phase of inflammation. Their role in atherosclerosis, a chronic inflammatory vascular disease, has been largely unexplored. Using a mouse model of atherosclerosis, we found that CXCL5 expression was upregulated during disease progression, both locally and systemically, but was not associated with neutrophil infiltration. Unexpectedly, inhibition of CXCL5 was not beneficial but rather induced a significant macrophage foam cell accumulation in murine atherosclerotic plaques. Additionally, we demonstrated that CXCL5 modulated macrophage activation, increased expression of the cholesterol efflux regulatory protein ABCA1, and enhanced cholesterol efflux activity in macrophages. These findings reveal a protective role for CXCL5, in the context of atherosclerosis, centered on the regulation of macrophage foam cell formation.

Authors

Anthony Rousselle, Fatimunnisa Qadri, Lisa Leukel, Rüstem Yilmaz, Jean-Fred Fontaine, Gabin Sihn, Michael Bader, Amrita Ahluwalia, Johan Duchene

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Figure 1

Upregulation of CXCL5 in atherosclerosis.

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Upregulation of CXCL5 in atherosclerosis. (A) Assessment of CXCL5 mRNA (...
(A) Assessment of CXCL5 mRNA (blue triangles) and protein (red triangles) expression during the progression of atherosclerosis in aortas and plasma of Apoe–/– mice, respectively (n = 6–8 per time point), fed a WD for the indicated time. Apoe–/– mice fed a CD were used as controls. (B) Aortic Cxcl1, Cxcl2, and Cxcl5 mRNA and (C) plasma CXCL5 protein expression was measured in Apoe–/– mice fed CD or WD for 12 weeks (n = 8 mice per group). WT mice fed CD for 12 weeks were used as controls. (D) Assessment of Cxcl5 mRNA in aortas of WT mice (n = 6–8 per time point) fed WD. WT mice fed CD were used as controls. (E–G) HUVECs were subjected to high or low LSS and stimulated with (E) oxidized LDL (n = 3) or (F and G) IL-1β (n = 6). (E and F) CXCL8 and CXCL6 mRNA expression and (G) protein release were determined. (A–G) mRNA and protein levels were measured by qPCR and ELISA, respectively. Data are mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001.